title: Molecular mechanisms linking the evolutionary conserved TORC1-Sch9 nutrient signalling branch to lifespan regulation in Saccharomyces cerevisiae.
abstract: The knowledge on the molecular aspects regulating ageing in eukaryotic organisms has benefitted greatly from studies using the budding yeast Saccharomyces cerevisiae. Indeed, many aspects involved in the control of lifespan appear to be well conserved among species. Of these, the lifespan-extending effects of calorie restriction (CR) and downregulation of nutrient signalling through the target of rapamycin (TOR) pathway are prime examples. Here, we present an overview on the molecular mechanisms by which these interventions mediate lifespan extension in yeast. Several models have been proposed in the literature, which should be seen as complementary, instead of contradictory. Results indicate that CR mediates a large amount of its effect by downregulating signalling through the TORC1-Sch9 branch. In addition, we note that Sch9 is more than solely a downstream effector of TORC1, and documented connections with sphingolipid metabolism may be particularly interesting for future research on ageing mechanisms. As Sch9 comprises the yeast orthologue of the mammalian PKB/Akt and S6K1 kinases, future studies in yeast may continue to serve as an attractive model to elucidate conserved mechanisms involved in ageing and age-related diseases in humans.
authors.affiliation: Functional Biology, KU Leuven, Heverlee, Belgium.
authors.forename: Erwin
authors.initials: E
authors.lastname: Swinnen
authors.forename: Ruben
authors.initials: R
authors.lastname: Ghillebert
authors.forename: Tobias
authors.initials: T
authors.lastname: Wilms
authors.forename: Joris
authors.initials: J
authors.lastname: Winderickx
mesh_terms: D000375:Aging; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C530964:SCH9 protein, S cerevisiae
keywords: Sch9; TORC1; aging; calorie restriction; chronological life span; signalling